Swelling-activated chloride channels in cardiac physiology and pathophysiology

Characteristics and functions of the cardiac swelling-activated Cl current (I-Cl,I-swell) are considered in physiologic and pathophysiologic settings. I-Cl,I-swell is broadly distributed throughout the heart and is stimulated not only by osmotic and hydrostatic increases in cell volume, but also by agents that alter membrane tension and direct mechanical stretch. The current is outwardly rectifying, reverses between the plateau and resting potentials (E-m), and is time-independent over the physiologic voltage range. Consequently, I-Cl,I-swell shortens action potential duration, depolarizes E-m, and acts to decrease cell volume. Because it is activated by stimuli that also activate cation stretch-activated channels, I-Cl,I-swell should be considered as a potential effector of mechanoelectrical feedback. I-Cl,I-swell is activated in ischemic and non-ischemic dilated cardiomyopathies and perhaps during ischemia and reperfusion. I-Cl,I-swell plays a role in arrhythmogenesis, myocardial injury, preconditioning, and apoptosis of myocytes. As a result, I-Cl,I-swell potentially is a novel therapeutic target. (C) 2003 Elsevier Science Ltd. All rights reserved.